Effects of amino acids, especially taurine and gamma-aminobutyric acid (GABA), on analgesia and calcium depletion induced by morphine in mice.
The analgesic effect of morphine was antagonized in mice by intracerebroventricular pretreatment with taurine, gamma-aminobutyric acid (GABA) or glycine and was potentiated by ethylene glycol tetra-acetic acid (EGTA) but not altered by L-glutamate or L-aspartate. The potentiation of morphine analgesia by EGTA was reversed by a concentration of taurine that did not alter the tail-flick response. The selective depletion of 45Ca2+ from synaptic vesicles observed with morphine administration was significantly inhibited by taurine injection (1.2 mumol/brain, i.vt.) but was not altered by the same dose of GABA. Inhibition of ATP-dependent 45Ca2+ uptake in synaptosomes by morphine was also completely reversed by taurine (10(-2)M which by itself did not alter 45Ca2+ uptake. These results suggest that antagonism of morphine analgesia by taurine may be caused by blockade of the morphine-induced inhibition of both ATP-dependent synaptosomal 45Ca2+ uptake and changes in synaptic vesicular 45Ca2+ localization, while the antagonism by GABA was not associated with synaptosomal Ca2+.
D000596:Amino Acids / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000596:Amino Acids; D013654:Taurine; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D002118:Calcium